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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05959850




Registration number
NCT05959850
Ethics application status
Date submitted
17/07/2023
Date registered
25/07/2023
Date last updated
7/09/2023

Titles & IDs
Public title
A Double-blind Randomised, Placebo-controlled Clinical Trial to Test Ambroxol Treatment in ALS
Scientific title
AMBroxol Therapy for ALS (AMBALS) Trial: a Double-blind, Randomised, Placebo-controlled Phase 2 Clinical Trial of Ambroxol for ALS
Secondary ID [1] 0 0
FLO-AMB-01
Universal Trial Number (UTN)
Trial acronym
AMBALS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ambroxol
Treatment: Drugs - Placebo

Experimental: Experimental: Active - Ambroxol taken 3x daily. Variation in doses as follow-up progresses. For detailed information, see Intervention Description.

Placebo Comparator: Placebo Comparator: Control - Glucose Placebo, taken 3x daily. Variation in doses as follow-up progresses. For detailed information, see Intervention Description.


Treatment: Drugs: Ambroxol
Participants in the study will receive varying doses of ambroxol in solution, 3 times per day. Doses will be increased pending a safety review, up to a maximum of 1260mg/day. Blood tests will be conducted weekly to assess tolerance. Compliance will be monitored by returning used bottles. The study will last 32 weeks, including 24 weeks of drug administration and follow-up visits. After the final follow-up, there will be an end of study safety visit occurring 4 weeks later. The total time of participation will be 32 weeks. This includes a screening visit up to 4 weeks prior to Baseline, then a Baseline visit, followed by 24 weeks of follow-up (3x in clinic follow-up visits). These 24 weeks will be the drug administration period, meaning that the total duration of drug administration is 24 weeks. Following this drug administration and follow-up period, there will be an EoS safety-follow up visit that will occur 4 weeks after the final follow-up visit (28 weeks from baseline).

Treatment: Drugs: Placebo
Participants randomised to the control arm will receive a placebo for the duration of the study. The placebo will look and taste like ambroxol, but will have no active ingredient. Participants will not be told which arm they have been randomised to. The placebo will primarily be a glucose solution, however it will also have flavouring (e.g. bitters) and colouring, so as to make it look and taste like ambroxol, to maintain blinding.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to event
Timepoint [1] 0 0
Time to event for a maximum of 24 weeks from baseline
Secondary outcome [1] 0 0
ALS functional rating score-revised (ALSFRS-R)
Timepoint [1] 0 0
24 weeks from Baseline
Secondary outcome [2] 0 0
Motor unit number estimation (MUNIX)
Timepoint [2] 0 0
24 weeks from Baseline
Secondary outcome [3] 0 0
Split Hand Index (SI)
Timepoint [3] 0 0
24 weeks from Baseline
Secondary outcome [4] 0 0
Neurophysiology Index (NPI)
Timepoint [4] 0 0
24 weeks from Baseline
Secondary outcome [5] 0 0
Kings staging system
Timepoint [5] 0 0
24 weeks from Baseline
Secondary outcome [6] 0 0
Muscle strength assessment as measured by the Medical Research Council (MRC) Scale for Muscle Strength
Timepoint [6] 0 0
24 weeks from Baseline
Secondary outcome [7] 0 0
Respiratory function (FVC) as measure by a Spirometer
Timepoint [7] 0 0
24 weeks from Baseline
Secondary outcome [8] 0 0
Survival
Timepoint [8] 0 0
24 weeks from Baseline
Secondary outcome [9] 0 0
Serum NFL levels
Timepoint [9] 0 0
24 weeks from Baseline
Secondary outcome [10] 0 0
Assessment of Quality of Life (AQoL)
Timepoint [10] 0 0
24 weeks from Baseline

Eligibility
Key inclusion criteria
1. Must have given written informed consent before any study related assessments are
performed and must be able to understand purpose of the study, including any possible
risks and adverse events.

2. ALS as diagnosed according to the recently proposed Gold Coast diagnostic criteria.

3. First symptom of ALS less than or equal to 18 months prior to screening. The
qualifying first symptoms of ALS are limited to manifestations of weakness in
extremity, bulbar, or respiratory muscles. Cramps, fasciculations, or fatigue should
not be taken in isolation as a first symptom of ALS.

4. Forced vital capacity (FVC) greater than or equal to 60% of predicted value as
adjusted for gender, height and age at the Screening Visit.

5. Male or female patients aged 18 years or greater (inclusive) and less than 85 years at
the time of ALS diagnosis.

6. Able to swallow liquid.

7. Able to perform reproducible pulmonary function tests

8. Female patients must be post-menopausal or sterilized or must not be breastfeeding,
have no intention to become pregnant during the study, and use acceptable methods of
contraception or abstain from intercourse.

9. Male patients who have not had a vasectomy and confirmed zero sperm count must agree
after receiving the first dose of study drug either to use acceptable methods of
contraception or abstain from intercourse.

10. If on riluzole, stable dosing for 30-days prior to screening.

11. Pre-study ALSFRS-R progression between disease onset and screening of greater than or
equal to 0.5 points/month (calculated by ALSFRS-R total score decline from 48 divided
by the months since onset of ALS symptoms).
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Use of non-invasive ventilation (NIV) support for ALS only or gastrostomy tube at time
of screening.

2. Exposure to investigational drug within 12-weeks prior to screening.

3. At screening of any medically significant cardiac, pulmonary, GI, musculoskeletal, or
psychiatric illness that might interfere with the patient's ability to comply with
study procedures or that might confound the interpretation of clinical safety or data.

4. Patient with a history of significant other major medical conditions based on the
Investigator's judgment.

5. Based on the investigator's judgment, patients who may have difficulty complying with
the protocol and/or any study procedures.

6. Any person who is an employee or an Investigator or Sponsor, or an immediate relative
of an Investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/06/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS,VIC
Recruitment hospital [1] 0 0
Brain and Mind Centre - Sydney
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Sydney
Recruitment hospital [3] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [4] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [5] 0 0
Calvary Health Care Bethlehem - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Sydney
Recruitment postcode(s) [2] 0 0
2139 - Sydney
Recruitment postcode(s) [3] 0 0
5042 - Adelaide
Recruitment postcode(s) [4] 0 0
7250 - Launceston
Recruitment postcode(s) [5] 0 0
3162 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
The Florey Institute of Neuroscience and Mental Health
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Mobius Medical Pty Ltd.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The University of Queensland
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Ambroxol is a simple cough medicine that is predicted to slow ALS disease progression. This
study aims to investigate if ambroxol in high doses is effective in treating ALS. This study
will be carried out across 5 research sites in Australia (2 NSW, 1 VIC, 1 SA and 1 TAS),
where newly diagnosed ALS patients will be asked to participate. Participation will be over a
32-week period, where they will come in for a 4-week screening, 24-week treatment, and 4-week
end of study safety follow-up period. The participants will receive either the placebo or
drug solution that they will take three times a day, up-dosing each week until they reach the
maximum dose or highest dose they can tolerate. Throughout the study their disease
progression will be assessed using tests, questionnaires, and blood biomarkers.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05959850
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bradley Turner
Address 0 0
The Florey Institute of Neuroscience and Mental Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Bradley Turner
Address 0 0
Country 0 0
Phone 0 0
+61 3 9035 6521
Fax 0 0
Email 0 0
bradley.turner@florey.edu.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05959850